DESCRIPTION (Taken from the applicant's abstract): This application is focused on the performance of two prospective, multicentered trials in children with juvenile rheumatoid arthritis (JRA). In addition, this career development grant is intended to enhance the ability of many pediatric rheumatology centers in North America to perform trials to determine the efficacy and safety of currently used but untested and also newly developed drugs in children with JRA by increasing the ability of the principal investigator (PI) to focus on the direction and coordination of the efforts of the Pediatric Rheumatology Collaborative Study Group (PRCSG) of which the PI is the chairman. The PRCSG is a consortium of over 45 academic pediatric rheumatology centers that have performed over 30 trials in children with JRA. Trial 1: Osteopenia is a significant and frequent complication of JRA. This research proposal includes a prospective, randomized, multicenter, placebo-controlled trial (RCT) to determine the efficacy of daily oral calcium supplementation (1000 mg/day of calcium carbonate) for two years to increase total body bone mineral density (TB BMD) by 10% (1.5 SD) compared to placebo treatment. In addition, the persistence of the treatment effect will be determined for 1.5 years after the RCT. This will be the first longitudinal study of bone mineralization in JRA and the control group will demonstrate the natural history of bone mineralization. Trial 2: This research proposal also includes a prospective, randomized, actively controlled, open clinical trial to determine the efficacy of combination drug therapy to induce prolonged drug-free remission in children with severe systemic JRA (sJRA). Patients will be enrolled early in the disease course but eligibility criteria will select those with a 115% risk of developing severe, erosive polyarthritis. One therapy regimen is composed of intravenous methylprednisolone for 3 consecutive days, intravenous cyclophosphamide on the third day, and up to 20 mg/M2/wk of methotrexate. The second pulse therapy regimen is identical to the first, except no cyclophosphamide is given. Up to 5 cycles of these regimens may be given over a 9-month period. Patients in both groups may also receive background medications including 1 non-steroidal anti-inflammatory drug and up to 0.5 mg/kg/d of oral prednisone. The short and intermediate (0-18 months) safety of these treatment regimens will be compared. Long-term goals: 1. Assess the efficacy and safety of current and emerging pharmacologic and biologic treatments as adjunctive therapy to calcium in JRA patients with osteopenia. 2. Determine the long-term efficacy and safety of these treatment regimens in sJRA.